rTMS and Botulinum Toxin in Primary Cervical Dystonia

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Primary cervical dystonia (PCD) is the most common form of focal dystonia. PCD is frequently reported as a source of disability, decreased quality of life, and social stigma. Botulinum toxin (BoNT) is the gold standard treatment for PCD. The average duration of benefits from BoNT injections was about 9.5 weeks and BoNT treatment is known to provide only pure symptomatic benefits and does not seem to modify the disease pathophysiology.

The investigator plans to use repetitive transcranial magnetic stimulation (rTMS) therapy as an adjunctive therapy in combination with BoNT injections as a novel approach to treat PCD. The primary goal of this study is to compare standard treatment with BoNT versus BoNT combined with a two week course of rTMS.

rTMS refers to the application of transcranial magnetic stimulation (TMS) pulses to a specific target at predefined stimulation parameters. Repeated sessions of rTMS therapy have been demonstrated to induce cumulative persistent benefits that can last weeks after the conclusion of the rTMS sessions

The central hypothesis of this study is that rTMS therapy in PCD can potentiate the effects of BoNT injections. With the current standard treatment, the peak-dose benefits seen with BoNT are seen at about 4-6 weeks after the administration of injections. The investigator will introduce a 1 week course of rTMS around 2-8 weeks before or after BoNT or T1). The investigator will examine the effects of combined therapy at 10 weeks after BoNT and 12 weeks after BoNT injections follow-up.

Repetitive TMS will be delivered over each cerebellar hemisphere, using a NeuroStar TMS therapy system. The coil will be positioned 3 cm lateral to the inion on the line joining the inion and the external auditory meatus. The coil position will be marked on the skin. 900 pulses will be delivered consecutively to each side with a frequency of 1 Hz and at an intensity of 90% of the resting motor threshold (RMT) for a total duration of 15 min for each cerebellar hemisphere. The RMT will be defined as the lowest stimulation intensity required to evoke a 50 μV potential in a target muscle. Constant coil position will be continuously monitored during the experiment. A similar protocol will be observed for the contralateral cerebellum. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.

Other: Craniocervical Dystonia Questionnaire (CDQ-24)

All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.

Other: Cerebellar-brain Inhibition (CBI)

All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Procedure: Botulinum toxin injections

All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care

Sham Comparator: Sham rTMS Stimulation

Patients will undergo the same procedure for identifying stimulus location used in patients receiving real rTMS. Simulated rTMS will be administered using sham NeuroStar TMS therapy system coil which produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been suggested to provide more effective blinding compared to other methods use in previous controlled studies. In addition, this group will have the following performed: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) test, Cerebellar-brain Inhibition (CBI) measurement, and Craniocervical Dystonia Questionnaire (CDQ-24) questionnaire to fill out.

Device: Sham NeuroStar TMS therapy

Same procedure as real rTMS without stimulating the cerebral cortex.

Other: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

All participants will receive a clinical assessment of dystonia severity by using the TWSTRS test.

Other: Craniocervical Dystonia Questionnaire (CDQ-24)

All participants will fill out the Craniocervical Dystonia Questionnaire (CDQ-24) quality of life questionnaire.

Other: Cerebellar-brain Inhibition (CBI)

All participants will have a measure of the cerebellar-brain inhibition(CBI) which will be conducted by using a TMS device determining the ability of the coil to activate the cerebellum.

Procedure: Botulinum toxin injections

All participants will receive Botulinum toxin(BoNT) injections as part of their standard of care

A clinical assessment of dystonia severity will be conducted at each study visit using the TWSTRS. Videos will be taken of the subjects at baseline, 6 weeks, 10 weeks, and 12 week which will be scored by two independent blinded raters. The TWSTRS is a widely accepted composite rating scale for PCD with subscales for clinical severity, functional disability, and associated pain. Higher scores represent greater impairment and scores range from 0-87.

A measure of the cerebellar-brain inhibition(CBI) will be conducted using a TMS device determining the ability of the coil to activate the cerebellum. The time course of effects on CBI will be measured at baseline, 6 weeks, and 12 weeks and determine if they correlate with clinical scoring of PCD symptoms.

Quality of life as assessed by Craniocervical Dystonia Questionnaire [ Time Frame: Baseline to 12 Weeks ]

The Craniocervical Dystonia Questionnaire (CDQ-24) is a patient-rated health related quality of life (HR-QoL) measure for craniocervical dystonia. It is composed of 24 items, forming 5 subscales: stigma, emotional well-being, pain, activities of daily living, and social/ family life. Items are rated on a 5-point scale. Each item consists of five statements representing increasing severity of impairment, scored from 0 to 4. Subjects will be instructed to indicate how they have felt during the past two weeks because of dystonia by selecting one of the five statements for each item. Subjects will also rate their symptoms before and after stimulation using a 7-point nominal scale: 1) excellent, 2) very good, 3) good, 4) average, 5) slightly worse than usual, 6) bad or 7) very bad. Videos will be taken of the subjects at baseline, 6 weeks, 10 weeks, and 12 weeks which will be scored by two independent blinded raters.

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Layout table for eligibility information

Ages Eligible for Study:

30 Years to 75 Years (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of PCD in accordance with the Consensus Statement of the Movement Disorder Society